Project Summary The rapid construction of complex carbon-carbon double bonds via olefin-olefin metathesis has revolutionized the synthesis of biologically active organic molecules. Conversely, the analogous carbon-olefin metathesis reaction has received little attention until very recently. The mechanistic studies presented herein will focus on understanding and improving Fe(III)-catalyzed carbonyl-olefin metathesis?a new approach for the construction of cycloalkenes. It is our hypothesis that the success of this reaction hinges upon Fe(III)-mediated formation of intermediate oxetane via a [2+2]-cycloaddition followed by Fe(III)-mediated cycloreversion to the metathesis product, and that the characterization of this reactivity will reveal new avenues of reactivity. To study this system, synthetic, spectroscopic, kinetic, and computational techniques will be employed to characterize the role of Fe(III), the resting state of the catalytic cycle, and the turnover-limiting step. These data will be used to determine the interplay of Lewis acid catalyst, solvent, and additives necessary for effective ring-closing metathesis. In the second portion of the proposed work, initial synthetic studies show that the operating catalytic cycle can vary greatly as a function of substrate structure, unveiling a wide array of new reactivity. Simple modifications to the carbonyl and olefin metathesis partners can not only change the operating mechanism, but dramatically alter reaction outcomes. To examine these substrate-dependent perturbations, a series of synthetic models will be employed as representative examples of five classes of substrate that display alternative reactivity under carbonyl-olefin metathesis conditions, involving alkyl and aryl ketones as well as prenyl and styrenyl olefins. Additionally, data obtained from the characterization of these cycloalkane-forming substrates will be employed in the development of ring-opening carbonyl olefin metathesis?the mechanistic reverse of the established methodology. Overall, these rigorous mechanistic studies will catalogue the factors critical to concise reaction design, enhancing the use of carbonyl-olefin metathesis in the construction of medicinally important molecules.